miR-19 promotes development of renal fibrosis by targeting PTEN-mediated epithelial-mesenchymal transition.

In recent years, it has been found that miRNA may play an important role in the field of gene regulation; miRNAs can participate in the regulation of various physiologic processes such as cell differentiation, proliferation, apoptosis, metabolism, and insulin secretion by regulation of target genes. The purpose of this study is to observe the relationship between the expression of miR-19 and renal fibrosis, to analyze the regulatory effect of miR-19 on renal tubular EMT, and to reveal its role and working mechanism in renal fibrosis. We found that the expression of miR-19 was significantly increased in peripheral blood of patients with renal fibrosis, in renal tissue of unilateral ureteral occlusion (UUO) mice, and in NRK-52E cells treated with TGF-β1. Overexpression of miR-19 could decrease the expression of E-cadherin and increase the expression of α-SMA and fibronectin, while inhibition of miR-19 reverses TGF-β1-induced EMT. Further studies revealed that miR-19 could inhibit its expression by binding to the 3'-UTR of PTEN. MiR-19 inhibitor or Akt inhibitor blocks phospho-Akt by TGF-β1, and Akt inhibitors block miR-19 mimic-induced EMT. In UUO mice, overexpression of miR-19 promoted the development of renal fibrosis, while inhibition of miR-19 expression produced the opposite result. These results indicate that abnormal expression of miR-19 is associated with renal fibrosis. Moreover, miR-19 activates the Akt signaling pathway by targeting PTEN, and induces EMT in renal tubular epithelial cells, thereby promoting renal fibrosis. IJCEP